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<p>Dosage tolerance is one of the translational challenges of using metformin (Met) in brain therapeutics. This paper presents metal–organic framework (MOF)-74-Mg nanocarriers (NCs) for intranasal (IN) delivery of brain-specific agents with a prolonged release time. We confirmed their excellent biocompatibility (5&#xa0;mg/mL) and intrinsic fluorescence properties (370/500&#xa0;nm excitation/emission peak) in Neuro-2A cells. This NC exhibited a high Met loading rate (10% wt/wt) and a sustained and prolonged release pattern of Met (90% release in 16&#xa0;h) in Dulbecco’s Modified Eagle Medium. We observed an optimal brain accumulation of Met-MOF (9% of the injected dosage) 8&#xa0;h after IN injection. This percentage is at least 82 times higher than oral administration. Confocal imaging demonstrated significantly higher uptake of Met-MOF, 45&#xa0;min after IN injection, by 79–85% neurons and 93–97% microglia than astrocytes and oligodendrocytes across 5xFAD mouse brain regions, including hippocampus and striatum. These results suggest MOF-74-Mg is a potential NC for high brain Met accumulation, real-time imaging, and prolonged and sustained release of Met and other neurotherapeutic agents that are challenging to deliver using traditional carriers and administration routes.</p>

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Intranasal delivery of metformin using metal–organic framework (MOF)-74-Mg nanocarriers

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月18日

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  • Muzhaozi Yuan,
  • Zongsu Han,
  • Yogish Somayaji,
  • Nguyen Nguyen,
  • Hanwen Hu,
  • Leelavathi N. Madhu,
  • Sahithi Attaluri,
  • Maheedhar Kodali,
  • Yihao Yang,
  • Yu-Chuan Hsu,
  • Avik Ahuja,
  • Rahul Srinivasan,
  • Jean-Philippe Pellois,
  • Hong-Cai Zhou,
  • Ashok K. Shetty,
  • Ya Wang

摘要

Dosage tolerance is one of the translational challenges of using metformin (Met) in brain therapeutics. This paper presents metal–organic framework (MOF)-74-Mg nanocarriers (NCs) for intranasal (IN) delivery of brain-specific agents with a prolonged release time. We confirmed their excellent biocompatibility (5 mg/mL) and intrinsic fluorescence properties (370/500 nm excitation/emission peak) in Neuro-2A cells. This NC exhibited a high Met loading rate (10% wt/wt) and a sustained and prolonged release pattern of Met (90% release in 16 h) in Dulbecco’s Modified Eagle Medium. We observed an optimal brain accumulation of Met-MOF (9% of the injected dosage) 8 h after IN injection. This percentage is at least 82 times higher than oral administration. Confocal imaging demonstrated significantly higher uptake of Met-MOF, 45 min after IN injection, by 79–85% neurons and 93–97% microglia than astrocytes and oligodendrocytes across 5xFAD mouse brain regions, including hippocampus and striatum. These results suggest MOF-74-Mg is a potential NC for high brain Met accumulation, real-time imaging, and prolonged and sustained release of Met and other neurotherapeutic agents that are challenging to deliver using traditional carriers and administration routes.